Ageing (British English) or aging (American English) is the process of becoming older. In the narrow sense, the term refers to biological ageing of human beings, animals and other organisms. In the broader sense, ageing can refer to single cells within an organism (cellular senescence) or to the population of a species (population ageing).

In humans, ageing represents the accumulation of changes in a human being over time,[1][2] encompassing physical, psychological, and social change. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Ageing is among the largest known risk factors for most human diseases:[3] of the roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes.

The causes of ageing are unknown; current theories are assigned to the damage concept, whereby the accumulation of externally induced damage (such as DNA point mutations) may cause biological systems to fail, or to the programmed ageing concept, whereby internal processes (such as DNA telomere shortening) may cause ageing.

The discovery, in 1934, that calorie restriction can extend lifespan twofold in rats, and the existence of potentially immortal species such as Hydra, have motivated research into delaying and preventing ageing.

Human beings and members of many other species necessarily experience ageing and mortality. In contrast, some species can be considered immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability with which they avoid dying of old age.

Even within humans and other mortal species, there are arguably cells with the potential for immortality: cancer cells which have lost the ability to die such as the HeLa cell line, stem cells, and specifically germ cells (producing ova and spermatozoa).[4] In artificial cloning, adult cells can be rejuvenated back to embryonic status and then used to grow a new tissue or animal without ageing.[5] Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961).

After a period of near perfect renewal (in humans, between 20 and 35 years of age), ageing is characterised by the declining ability to respond to stress, increasing homeostatic imbalance and the increased risk of disease. This currently irreversible series of changes inevitably ends in death.

Around age 50, hair turns grey in Caucasoids.[7] Many men are affected by balding, and women enter menopause.

Ageing furthermore is among the greatest known risk factors for most human diseases.[3] Specifically, age is a major risk factor for most common neurodegenerative diseases, including Mild cognitive impairment, Alzheimer's disease, cerebrovascular disease, Parkinson's disease and Lou Gehrig's disease. Research has focused in particular on memory and ageing and has found decline in many types of memory with ageing, but not in semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until the late adulthood.[8] Early studies on changes in cognition with age generally found declines in intelligence in the elderly, but studies were cross-sectional rather than longitudinal and thus results may be an artefact of cohort rather than a true example of decline. However, longitudinal studies could be confounded due to prior test experience.[9]Intelligence may decline with age, though the rate may vary depending on the type and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in rate of cognitive decline may therefore be explained in terms of people having different lengths of life.[10] There are changes to the brain: though neuron loss is minor after 20 years of age there is a 10% reduction each decade in the total length of the brain's myelinatedaxons.[11]

Age can result in communication barriers, such as due to hearing loss and visual impairment.[12] Sensory impairments include hearing and vision deficits. Changes in cognition, hearing, and vision are associated with healthy ageing and can cause problems when diagnosing dementia and aphasia due to the similarities.[13] Common conditions that can increase the risk of hearing loss in elderly people are high blood pressure, diabetes or the use of certain medications harmful to the ear.[14]Hearing aids are commonly referred to as personal amplifying systems, which can generally improve hearing by about 50%. In visual impairment, non-verbal communication is reduced, which can lead to isolation and possible depression. Macular degeneration is a common cause of vision loss in elderly people. This degeneration is caused by systemic changes in the circulation of waste products and growth of abnormal vessels around the retina causing the photoreceptors not to receive proper images.[15]

A distinction can be made between "proximal ageing" (age-based effects that come about because of factors in the recent past) and "distal ageing" (age-based differences that can be traced back to a cause early in person's life, such as childhood poliomyelitis).[10]

Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die from age-related causes. In industrialised nations, the proportion is much higher, reaching 90%.[16][17][18]

At present, the biological basis of ageing is unknown. Even in relatively simple and short-lived organisms, the mechanisms of ageing remain to be elucidated. Less is known about mammalian ageing, in part due to the much longer lives in even small mammals such as the mouse (around 3 years). A primary model organism for studying ageing is the nematodeC. elegans, thanks to its short lifespan of 2–3 weeks, the ability to easily perform genetic manipulations or suppress gene activity with RNA interference, and other factors.[19] Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.[20]

Biological theories of ageing in humans fall into two main categories: programmed aging theories and damage theories. The programmed ageing theories imply that ageing follows a biological timetable, perhaps a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. The damage theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of aging.[21]

There are four main metabolic pathways which can influence the rate of ageing: caloric restriction; the insulin/IGF-1-like signalling pathway; the activity levels of the electron transport chain in mitochondria and (in plants) in chloroplasts, and the FOXO3/Sirtuin pathway. It is likely that most of these pathways affect ageing separately, because targeting them simultaneously leads to additive increases in lifespan.[22]

The rate of ageing varies substantially across different species, and this, to a large extent, is genetically based. Numerous species show very low signs of ageing ("negligible senescence"), the best known being trees like the bristlecone pine (however Hayflick states that the bristlecone pine has no cells older than 30 years), fish like the sturgeon and the rockfish, invertebrates like the hard clam (known as quahog in New England) and the sea anemone[23] and lobster.[24][25] The genetic aspect has also been demonstrated in studies of centenarians.

In laboratory settings, researchers have demonstrated that selected alterations in specific genes can extend lifespan quite substantially in nematodes, less so in fruit flies and less again in mice. Some of the targeted genes have homologues across species and in some cases have been associated with human longevity.[26]

Telomere theory: In humans and other animals, cellular senescence has been attributed to the shortening of telomeres at each cell division; when telomeres become too short, the cells die. The length of telomeres is therefore the "molecular clock", predicted by Hayflick. This agrees with the 'ageing-clock theory' which suggests that an ageing sequence is built into the operation of the nervous or endocrine system of the body. In rapidly dividing cells, shortening of the telomeres would provide such a clock. This idea is in contradiction with the evolutionary based theory of ageing.[27][28]Telomeres have experimentally been shown to shorten with each successive cell division.[29] Shortened telomeres activate a mechanism that prevents further cell multiplication.[30][31] This may be particularly limiting to tissues such as bone marrow and the arterial lining where cell division occurs repeatedly throughout life.[32] The quantity of the hematopoietic stem cells that produce the blood components residing in the bone marrow of human beings have been found to decline with ageing.[33] Stem cells regenerative capacity is affected by the age of the recipient.[2] Importantly though, mice lacking telomerase enzyme do not show a dramatically reduced lifespan,[34] invalidating at least simple versions of the telomere theory of ageing. Laboratory mice may be an exception for the theory, as they have long hypervariable telomeres,[35] which prolong the period after which telomere shortening would affect life-span. However, wild mouse strains do not, and telomere length in these breeds is unrelated to lifespan[36]

Genetic ties to lifespan: A variation in the gene FOXO3A is known to have a positive effect on the life expectancy of humans, and is found much more often in people living to 100 and beyond - moreover, this appears to be true worldwide.[37] FOXO3A acts on the sirtuin family of genes which have also been shown to have a significant effect on lifespan, in yeast and in nematodes. Over-expression of the RAS2 gene increases lifespan in yeast by 30%.[38]

Diet (specifically, caloric restriction) has been shown to substantially affect lifespan in many animals, including the delay or prevention of many age-related diseases.[39] Typically, this involves caloric intake of 60–70% of what an ad libitum animal would consume, while still maintaining proper nutrient intake.[39] In rodents, this has been shown to increase lifespan by up to 50%;[40] this effect occurs for many other species besides mice, including species as diverse as yeast and Drosophila,[39] and likely includes primates as well.[39][41][42] There are two major studies of caloric restriction being performed in rhesus monkeys, one at the US National Institutes of Health, and the other at the University of Wisconsin-Madison.[41] The basis for caloric restriction remains unclear,[22] though it is likely mediated by nutrient-sensing pathways such as the mTOR pathway.[42] Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.[43] However, in his book How and Why We Age, Hayflick says that caloric restriction may not be effective in humans, citing data from the Baltimore Longitudinal Study of Aging which shows that being thin does not favour longevity.[need quotation to verify][44]

mTOR theory: mTOR, a protein that inhibits autophagy has been linked to ageing through the insulin signalling pathway. It has been found, in various model species, that caloric restriction leads to longer lifespans, an effect that is likely mediated by the nutrient-sensing function of the mTOR pathway.[42] mTOR functions through nutrient and growth cues leading scientists to believe that dietary restriction and mTOR are related in terms of longevity. When organisms restrict their diet, mTOR activity is reduced, which allows an increased level of autophagy. This recycles old or damaged cell parts, which increases longevity and decreases the chances of being obese. This is thought to prevent spikes of glucose concentration in the blood, leading to reduced insulin signalling. This has been linked to less mTOR activation as well. Therefore, longevity has been connected to caloric restriction and insulin sensitivity inhibiting mTOR, which in turns allows autophagy to occur more frequently. It may be that mTOR inhibition and autophagy reduce the effects of reactive oxygen species on the body, which damage DNA and other organic material, so longevity would be increased.[45]

Evolutionary theories: Many have argued that life-span, like other phenotypes, is selected. Traits that benefit early survival and reproduction will be selected for even if they contribute to an earlier death. Such a genetic effect is called the antagonistic pleiotropy effect when referring to a gene (pleiotropy signifying the gene has a double function - enabling reproduction at a young age but costing the organism life expectancy in old age) and is called the disposable soma effect when referring to an entire genetic programme (the organism diverting limited resources from maintenance to reproduction).[46] Some evidence is provided by oxygen-deprived bacterial cultures.[47] This would explain why the autosomal dominant disease, Huntington's disease, can persist even though it is inexorably lethal. Also, some of the genetic variants that increase fertility in the young are now known to increase cancer risk in the old. Such genes include p53[48] and BRCA1.[49] The biological mechanisms which regulate lifespan evolved several hundred million years ago.[20]

Reproductive-cell cycle theory: The idea that ageing is regulated by reproductive hormones that act in an antagonistic pleiotropic manner via cell cycle signalling, promoting growth and development early in life to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence (dyosis).[1][50] The endocrine dyscrasia that follows the loss of follicles with menopause, and the loss of Leydig and Sertoli cells during andropause, drive aberrant cell cycle signaling that leads to cell death and dysfunction, tissue dysfunction (disease) and ultimately death. Moreover, the hormones that regulate reproduction also regulate cellular metabolism, explaining the increases in fat deposition during pregnancy through to the deposition of centralized adiposity with the dysregulation of the HPG axis following menopause and during andropause (Atwood and Bowen, 2006). This theory, which introduced a new definition of aging, has facilitated the conceptualization of why and how aging occurs at the evolutionary, physiological and molecular levels.[1] In essence, this theory proposes that reproductive hormones not only regulate reproduction and metabolism, but also modulate the life and function of cells, and in so doing, the life of the organism, thereby tying reproduction, metabolism and longevity together in an evolutionary manner that allows for the continued survival of the species.

Autoimmune theory: The idea that ageing results from an increase in autoantibodies that attack the body's tissues. A number of diseases associated with ageing, such as atrophic gastritis and Hashimoto's thyroiditis, are probably autoimmune in this way. While inflammation is very much evident in old mammals, even SCID mice in SPF colonies still experience senescence.

DNA damage theory of ageing: Genetic damage has two types. Mutations are damages to the DNA sequence, while epimutation is damage to the DNA scaffolding which regulates gene expression in the cell. Both ultimately harm our health by causing abnormal gene expression. Some (epi-)mutations lead to cancers, which are the uncontrolled growth and division of cells. Lifelong studies of mice suggest that most mutations happen during embryonic and childhood development, when cells divide often, as each cell division is a chance for errors in DNA replication.[51] Known causes of cancer (radiation, chemical and viral) account for about 30% of the total cancer burden and for about 30% of the total DNA damage. DNA damage causes the cells to stop dividing or induces apoptosis, often affecting stem cell pools and hence hindering regeneration.[2] DNA damage is thought to be the common pathway causing both cancer and ageing. Viral infection would appear to be the most likely cause of the other 70% of DNA damage especially in cells that are not exposed to smoking and sun light. It has been argued, too, that intrinsic causes of DNA damage are more important drivers of ageing.[52][53][54]

Gene loss theory of ageing: It has been established that dogs lose approximately 3.3% of the DNA in their heart muscle cells annually while humans lose approximately 0.6% of their heart muscle DNA each year. These numbers are close to the ratio of the maximum longevities of the two species (120 years vs. 20 years, a 6/1 ratio). The comparative percentage is also similar between the dog and human for yearly DNA loss in the brain and lymphocytes. As stated by lead author, Bernard L. Strehler, "....genetic damage (particularly gene loss) is almost certainly (or probably the) central cause of aging."[55]

Accumulative-waste theory: The biological theory of ageing that points to a buildup in cells of waste products that presumably interfere with metabolism. Evidence supporting this theory is the presence of a waste product called lipofuscin leading to age pigment. Lipofuscin is formed by a complex reaction that binds fat in the cells to proteins. This waste accumulates in the cells as small granules and increases in size as a person ages[56]

Wear-and-tear theory: The very general idea that changes associated with ageing are the result of chance damage that accumulates over time.

Misrepair-accumulation theory: Wang et al.[60] suggests that ageing is the result of the accumulation of "misrepair". Important in this theory is the distinction between "damage" (a newly emerged defect before any repair has taken place) and "misrepair" (the defective structure after incorrect repair). The key points in this theory are:

There is no original damage left unrepaired in a living being. If damage were left unrepaired a life-threatening condition (such as bleeding, infection, or organ failure) would develop.

Misrepair is a consequence of a repair system which needs to achieve sufficiently quick repairs in situations of serious or repeated damage, to maintain the basic function of a structure, which is important for the survival of the living being.

Rapid, albeit flawed, repair increases the chance for the survival of the individual to the reproduction age, which is vital for the survival of the species. Therefore the misrepair mechanism is selected by nature due to its evolutionary advantage.

Since misrepair of a defective structure is invisible to the repair system, misrepair accumulates with time and causes the disorganisation of a structure (tissue, cell, or molecule); this disorganisation is the actual process of ageing.

Accumulation of misrepairs is focalized and self-accelerating. Focalized accumulation of misrepairs leads to the development of "spots" or "plaques" in a tissue, such as atherosclerotic plaques,[61] tumors,[62] and age spots in skin.[63] Thus, development of aging changes is inhomogeneous and self-accelerating.[64]

The misrepair-accumulation theory is useful for interpreting several aspects of aging and aging related diseases. Tissue fibrosis is a good example which cannot be explained by traditional aging theories.[clarification needed][65]

Premature aging is a consequence of mis-construction of tissues and organs during development caused by genetic disorders. The abnormality in tissue structure is the common point between premature aging and normal aging, and it links a defective development and a defective repair, the misrepair.[66]

The potential of longevity of an organism is hidden in its structural complexity. An organism has limited longevity because it has limited structural complexity.[clarification needed] Limited structural complexity and limited longevity are essential for the survival of a species.[67]

The misrepair mechanism appears to be essential for maintaining a sufficient number of individuals [clarification needed] in a species and maintaining the diversity of genome DNAs of a species. Thus the misrepair-accumulation theory is useful not only for understanding aging and cancer-development, but also for understanding longevity, adaptation,[68] and species evolution.[69] An overview on the advances and limitations of traditional aging theories is outlined in a recent review article.[70]

In a UNFPA report about aging in the 21st century, it highlighted the need to "Develop a new rights-based culture of aging and a change of mindset and societal attitudes towards ageing and older persons, from welfare recipients to active, contributing members of society." [72] UNFPA said that this "requires, among others, working towards the development of international human rights instruments and their translation into national laws and regulations and affirmative measures that challenge age discrimination and recognize older people as autonomous subjects." [72] Older persons make vast contributions to society including caregiving and volunteering. For example, "A study of Bolivian migrants who moved to Spain found that 69 per cent left their children at home, usually with grandparents. In rural China, grandparents care for 38 per cent of children aged under five whose parents have gone to work in cities." [72]

Population ageing is the increase in the number and proportion of older people in society. Population ageing has three possible causes: migration, longer life expectancy (decreased death rate) and decreased birth rate. Ageing has a significant impact on society. Young people tend to have fewer legal privileges (if they are below the age of majority), they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. Older people have different requirements from society and government, and frequently have differing values as well, such as for property and pension rights.[73]

In the 21st century, one of the most significant population trends is aging.[74] Currently, over 11% of the world’s current population are people aged 60 and older and the United Nations Population Fund (UNFPA) estimates that by 2050 that number will rise to approximately 22%.[72] Ageing has occurred due to development which has enabled better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy have risen. Life expectancy at birth is over 80 now in 33 countries. Ageing is a "global phenomenon," that is occurring fastest in developing countries, including those with large youth populations, and poses social and economic challenges to the work which can be overcome with "the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits." [75]

As life expectancy rises and birth rates decline in developed countries, the median age itself rises accordingly. According to the United Nations, this process is taking place in nearly every country in the world.[76] A rising median age can have significant social and economic implications, as the workforce gets progressively older and the number of old workers and retirees grows relative to the number of young workers. Older people generally incur more health-related costs than do younger people in the workplace and can also cost more in worker's compensation and pension liabilities.[77] In most developed countries an older workforce is somewhat inevitable. In the United States for instance, the Bureau of Labor Statistics estimates that one in four American workers will be 55 or older by 2020.[77]

Among the most urgent concerns of older persons worldwide is income security. This poses challenges for governments with ageing populations to ensure investments in pension systems continues in order to provide economic independence and reduce poverty in old age. These challenges vary for developing and developed countries. UNFPA stated that, "Sustainability of these systems is of particular concern, particularly in developed countries, while social protection and old-age pension coverage remain a challenge for developing countries, where a large proportion of the labour force is found in the informal sector." [72]

The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age. In order to elevate this pressure "social protection floors must be implemented in order to guarantee income security and access to essential health and social services for all older persons and provide a safety net that contributes to the postponement of disability and prevention of impoverishment in old age." [72]

It has been argued that population ageing has undermined economic development however there is no solid evidence to substantiate this. Evidence suggests that pensions, while making a difference to the well-being of older persons, also benefit entire families especially in times of crisis when there may be a shortage or loss of employment within households. A study by the Australian Government in 2003 estimated that "women between the ages of 65 and 74 years contribute A$16 billion per year in unpaid caregiving and voluntary work. Similarly, men in the same age group contributed A$10 billion per year." [72]

In the field of sociology and mental health, aging is seen in five different views: aging as maturity, aging as decline, aging as a life-cycle event, aging as generation, and aging as survival.[78] Positive correlates with aging often include economics, employment, marriage, children, education, and sense of control, as well as many others. The social science of aging includes disengagement theory, activity theory, selectivity theory, and continuity theory. Retirement, a common transition faced by the elderly, may have both positive and negative consequences.[79]

With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that,[75]

"A life-cycle approach to health care – one that starts early, continues through the reproductive years and lasts into old age – is essential for the physical and emotional well-being of older persons, and, indeed, all people. Public policies and programmes should additionally address the needs of older impoverished people who cannot afford health care."

Many societies in Western Europe and Japan have ageing populations. While the effects on society are complex, there is a concern about the impact on health care demand. The large number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in ageing societies can be organised under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.[80]

However, the annual growth in national health spending is not mainly due to increasing demand from ageing populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients.[81] A number of health problems become more prevalent as people get older. These include mental health problems as well as physical health problems, especially dementia.

It has been estimated that population ageing only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3 percent since 1970. In addition, certain reforms to the Medicare system in the United States decreased elderly spending on home health care by 12.5 percent per year between 1996 and 2000.[82]

Positive self-perception of health has been correlated with higher well-being and reduced mortality in the elderly.[83][84] Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status.[85] This finding is generally stronger for men than women,[84] though this relationship is not universal across all studies and may only be true in some circumstances.[85]

As people age, subjective health remains relatively stable, even though objective health worsens.[86] In fact, perceived health improves with age when objective health is controlled in the equation.[87] This phenomenon is known as the "paradox of ageing." This may be a result of social comparison;[88] for instance, the older people get, the more they may consider themselves in better health than their same-aged peers.[89] Elderly people often associate their functional and physical decline with the normal ageing process.[90][91]

The concept of successful ageing can be traced back to the 1950s and was popularised in the 1980s. Previous research into ageing exaggerated the extent to which health disabilities, such as diabetes or osteoporosis, could be attributed exclusively to age, and research in gerontology exaggerated the homogeneity of samples of elderly people.[92][93] Other research shows that even late in life, potential exists for physical, mental, and social growth and development.[94]

Traditional definitions of successful aging have emphasized absence of physical and cognitive disabilities.[95] In their 1987 article, Rowe and Kahn characterized successful aging as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement.[93]

Some researchers (specifically biogerontologists) who study the biology of ageing believe that the development of interventions which slow ageing is inevitable.[45] Several drugs and food supplements have been shown to retard or reverse the biological effects of ageing in animal models, but none has yet been proven to do so in humans.

Ronald A. DePinho, a cancer geneticist at the Dana-Farber Cancer Institute and Harvard Medical School, published a paper in Nature magazine in November 2010 which indicated that the organs of genetically altered mice, designed to activate telomerase after feeding them with a chemical,[clarification needed] were rejuvenated. Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver, intestines and brain, recuperated from their degenerated state. In this experiment mice were engineered to not produce telomerase naturally but after a chemical "switch" the system would then restore telomerase. Importantly, this chemical does not have the ability to produce telomerase in animals that are not genetically altered. Moreover, telomerase activation is also associated with the growth of cancerous tumours which could prevent anti-ageing treatments using this discovery.[96]

mTOR inhibition and the frequent activation of autophagy has been shown to increase longevity in model organisms such as yeast, flies and mice. mTor inhibition and autophagy have also been linked to insulin sensitivity and the reduction of reactive oxygen species (ROS) damage, which is another major proposed cause to ageing. It has become clear that autophagy activation in the body by mTOR inhibition increases longevity. mTOR inhibition reduces ROS damage by activating autophagy, which will recycle the damaged parts of cells and re use them for functioning parts. This process reduces ROS damage to a reasonable amount, therefore increasing longevity. mTOR inhibition has also been linked to other major ageing diseases. mTOR inhibition has helped treat neurodegenerative diseases like Alzheimer's in mice. It has also been used to reduce tumor growth in several cancers including renal, breast and several other rare cancers. Finally mTOR inhibition is also linked to reducing obesity and increasing immune function. The mTOR inhibition reduces the likelihood of diet induced and age induced obesity in mice, but in some cases led to glucose intolerance. Caloric restriction and exercise are two ways to activate autophagy and inhibit mTOR which can help resolve all of these common age related health issues.[45]

The cellular balance between energy generation and consumption (energy homeostasis) requires tight regulation during ageing. In 2011, it was demonstrated that acetylation levels of AMP-activated protein kinase change with age in yeast and that preventing this change slows yeast ageing.[97]

Caloric restriction substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases.[39] Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.[43]

Most known genetic interventions in C. elegans increase lifespan by 1.5 to 2.5-fold. As of 2009, the record for lifespan extension in C. elegans is a single-gene mutation which increases adult survival by tenfold.[20] The strong conservation of some of the mechanisms of ageing discovered in model organisms imply that they may be useful in the enhancement of human survival. However, the benefits may not be proportional; longevity gains are typically greater in C. elegans than fruit flies, and greater in fruit flies than in mammals. One explanation for this is that mammals, being much longer-lived, already have many traits which promote lifespan.[20]

Some research effort is directed to slow ageing and extend healthy lifespan.[98][99][100]

The US National Institute on Aging currently funds an intervention testing program, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice.[101] Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals and lax mouse husbandry conditions.[citation needed] The intervention testing program aims to address this by conducting parallel experiments at three internationally recognised mouse ageing-centres, the Barshop Institute at UTHSCSA, the University of Michigan at Ann Arbor and the Jackson Laboratory.

Prizes for extending lifespan and slowing ageing in mammals exist. The Methuselah Foundation offers the Mprize. Recently, the $1 Million Palo Alto Longevity Prize was launched. It is a research incentive prize to encourage teams from all over the world to compete in an all-out effort to "hack the code" that regulates our health and lifespan. It was founded by Joon Yun.[104][105][106][107][108]

^Wang-Michelitsch, Jicun; Michelitsch, Thomas (2015). "Cell transformation in tumor-development: a result of accumulation of Misrepairs of DNA through many generations of cells" 1505. p. 14. arXiv:1505.01375. Bibcode:arXiv:1505.01375.